Inflammasome and Its Therapeutic Targeting in Rheumatoid Arthritis

Inflammasome is a cytoplasmic multiprotein complex that facilitates the clearance of exogenous microorganisms or the recognition of endogenous danger signals, which is critically involved in innate inflammatory response. Excessive or abnormal activation of inflammasomes has been shown to contribute to the development of various diseases including autoimmune diseases, neurodegenerative changes, and cancers. Rheumatoid arthritis (RA) is a chronic and complex autoimmune disease, in which inflammasome activation plays a pivotal role in immune dysregulation and joint inflammation. This review summarizes recent findings on inflammasome activation and its effector mechanisms in the pathogenesis of RA and potential development of therapeutic targeting of inflammasome for the immunotherapy of RA.

Targeting Regulatory T Cells for Therapy of Lupus Nephritis

Lupus glomerulonephritis (LN) is a complex autoimmune disease characterized by circulating autoantibodies, immune-complex deposition, immune dysregulation and defects in regulatory T cell (Tregs). Treatment options rely on general immunosuppressants and steroids that have serious side effects. Approaches to target immune cells, such as B cells in particular, has had limited success and new approaches are being investigated. Defects in Tregs in the setting of autoimmunity is well known and Treg-replacement strategies are currently being explored. The aim of this minireview is to rekindle interest on Treg-targeting strategies. We discuss the existing evidences for Treg-enhancement strategies using key cytokines interleukin (IL)-2, IL-33 and IL-6 that have shown to provide remission in LN. We also discuss strategies for indirect Treg-modulation for protection from LN.

Lupus Eritematosus Sistemik pada Pria

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by presence of nucleus autoantibody and affected multiple organ. Systemic lupus erythematosus is more common in women than men with ratio 2:1 to 15:1. Men with SLE often have a more aggressive clinical course, lead to a poorer prognosis compared with women with SLE. Case Report: A man, 29 years old came to hospital with main complain joint pain increased since 1 week ago, accompanied with red spot on face, trunk, hands, foot, and back, hair loss, swollen leg, mouth ulcer, and fatique. Malar rash and discoid rash were identified from physical examination. From laboratorium, ANA profile was positive for RNP/Sm, Sm, dsDNA, and histone. Skin biopsy showed a lupus discoid. Conclusion: The patient was treated with pulse-dose methylprednisolone for 3 days and showed a good response clinically.

Lupus Eritematosus Sistemik pada Pria

Objective: Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving many systems. Highest incidence and prevalence of SLE is found in Northern America 23.2/100,000 population/year and 241/100,000 population. According to sex differences, SLE is predominantly occurs in women than men with ratio 15:1 to 22:1. This discrepancy often causes delay in diagnosing SLE in male patients. Method: Case report. Result: We reported a male patient aged 21 years with pain of his joints, hyperpigmentation lesions on his face, alopesia, oral ulcers and decrease of body weight. Laboratory results showed increases in AST, ALT and D-Dimer, and from ANA Profile examination we got several positives results such as RNP/Sm (RNP/Sm) (++), Sm (Sm) (+), Ro-52 recombinant (52) (+), PCNA (PCNA) (+), DsDNA (DNA) (+), Nucleosome (NUC) (+), Histone (HI) (++), Ribosomal-P-protein (RIB) (+++) dan AMA-M2 (M2) (+). This patient met SLE criteria based on ACR 1997, SLICC 2012 and EULAR/ACR 2018. Patient was given oral methyl prednisolone 16-16-8 mg and VTE prophylaxis with subcutaneous heparin 2x5000 IU. Conclusion: SLE occurs rarely in male patients than female patients and has more diverse manifestations.

Overall mortality

Systemic sclerosis is a highly morbid, complex autoimmune disease that is variable both in its phenotype and the attendant mortality driven by such manifestations. This review article synthesizes mortality data from the best available meta-analyses, subgroup analyses of single cohorts, and subjective comparisons of individual cohort studies, which in aggregate suggest that mortality in systemic sclerosis has been gradually improving over the past several decades. This review also summarizes the literature describing various risk factors for mortality in systemic sclerosis.

Vaskulitis pada Lupus Eritematosus Sistemik

AbstrakLupus Eritematosus Sistemik (LES) merupakan penyakit autoimun kompleks yang menyerang berbagai sistem tubuh. Salah satu manifestasi LES adalah vaskulitis, yaitu inflamasi pada dinding pembuluh darah. Vaskulitis sekunder akibat LES terjadi pada beberapa pasien LES dengan gambaran yang bervariasi. Gambaran vaskulitis yang tersering pada LES adalah vaskulitis kutaneus. Dilaporkan seorang perempuan 26 tahun yang telah dikenal dengan LES, datang dengan keluhan bintik-bintik merah di kedua tungkai dan lengan yang tidak gatal dan tidak nyeri. Dilakukan biopsi pada lesi kulit dengan hasil tampak pada jaringan kulit dengan epidermis yang mengalami atrofi, hyperkeratosis, ketotik plague, terdapat daerah dengan penebalan membrana basalis. Dibawah dermis tampak sebukan sel radang perivasikuler, terdapat limfosit dan beberapa leukosit PMN. Gambaran tersebut sesuai dengan gambaran discoid lupus erythematosus dan vaskulitis. Discoid lupus erythematosus merupakan salah satu bentuk dari lupus eritematosus kutaneus dan merupakan bentuk yang tersering. Pada kasus ini vaskulitis muncul menunjukkan kambuh atau aktifnya penyakit LES yang telah diderita pasien selama 2 tahun. Hal tersebut ditunjukkan dengan jumlah skor MEX SLEDAI 6 dan skor SLEDAI 12. Pasien diberikan terapi dengan metil prednisolon intravena 2x125 mg selama 3 hari serta hidroksiklorokuin 1x200 mg per oral. Respon yang baik terlihat pada hari rawatan keenam dengan berkurangnya manifestasi vaskulitis secara signifikan.Kata kunci: lupus eritematosus sistemik, vaskulitisAbstractSystemic lupus erythematosus (SLE) is a complex autoimmune disease involving many systems in one’s body. One of SLE manifestations is vasculitis, an inflammation of the vessel wall. Secondary vasculitis caused by SLE happened in few SLE patients with various manifestations. The most common SLE vasculitis is cutaneous vasculitis. It has been reported a female patient (26 years old) who was known with SLE, with red spots on both her legs and arms without feeling itchy or painful. Skin biopsy was done to the patient and the result was an appearance in skin tissue with the atrophic epidermis, hyperkeratosis, ketotic plague, thickening area of membrana basalis. In dermis underneath, was distributed inflammation cells perivascular, with lymphocyte and numerous PMN leukocyte. This appearance corresponds with discoid lupus erythematosus and vasculitis. Discoid lupus erythematosus is one most common cutaneous lupus erythematosus. In this case, the occurrence of vasculitis demonstrated an active disease of SLE. Disease activity was assessed with MEX SLEDAI and SLEDAI scores, which are 6 and 12 consecutively. The patient was given intravenous methylprednisolone 125 mg twice a day for 3 days and oral hydroxychloroquine 200 mg once daily. A good response was found in the sixth day with significant improvement of her skin lesions.Keywords: systemic lupus erythematosus, vasculitis

Epigenomics and Transcriptomics of Systemic Sclerosis CD4+ T cells reveal Long Range Dysregulation of Key Inflammatory Pathways mediated by disease-associated Susceptibility Loci

ABSTRACTSystem sclerosis (SSc) is a genetically complex autoimmune disease mediated by the interplay between genetic and epigenetic factors in a multitude of immune cells, with CD4+ T lymphocytes as one of the principle drivers of pathogenesis. In this study, we obtained DNA methylation and expression profiles of CD4+ T cells from 48 SSc patients and 16 healthy controls. Consequently, we identified 9112 and 3929 differentially methylated CpGs positions (DMPs) and differentially expressed genes (DEGs) respectively. These DMPs and DEGs are enriched in functional categories related to inflammation and T cell biology. Furthermore, correlation analysis identified 17,500 possible DMP-DEG interaction pairs within a window of 5 Mb, and utilizing promoter capture Hi-C data, we confirmed that 212 CD4+ T cel specific pairs of DMP-DEG physically interact involving CTCF. Finally, utilizing SSc GWAS data, we identified four important SSc-associated susceptibility loci, TNIP1 (rs3792783), GSDMB (rs9303277), IL12RB1 (rs2305743) and CSK (rs1378942), that physically interact with DMP-DEG pairs cg17239269-ANXA6, cg19458020-CCR7, cg10808810-JUND and cg11062629-ULK3 respectively. Overall, our study reveals a solid link between genetic, epigenetic and transcriptional deregulation in CD4+ T cells of SSc patients, providing a novel integrated view of SSc pathogenic determinants.

Psoriasis in pregnancy: A review

Psoriasis is a complex autoimmune disease, most commonly characterized by silvery scale erythematous plaque. During pregnancy, there is a physiologic change of immunology status, which shifts from an inflammatory state to an anti-inflammatory state, in order to avoid fetal rejection. As a result of this immunomodulatory changes, the majority of pregnant patients experience improvement of their psoriasis. The treatment of psoriasis in pregnancy can be challenging, mainly because there is only a few evidence-based studies. The objective of this paper is to review the relevant data on psoriasis in pregnancy and its treatment.

Interferons (IFN-A/-B/-G) Genetic Variants in Patients with Mixed Connective Tissue Disease (MCTD)

Mixed connective tissue disease (MCTD) is a rare complex autoimmune disease in which autoantigens are recognized by endosomal TLRs. Their activation induces a higher secretion of the type I interferons, IFN-γ and the up-regulation of the INF-inducible genes. The present study aimed to investigate whether SNPs that are located in the IFN-A, IFN-B, and IFN-G genes are associated with MCTD. 145 MCTD patients and 281 healthy subjects were examined for IFN-A, IFN-B, and IFN-G genetic variants by TaqMan SNP genotyping assay. ELISA determined IFN-α/-β/-γ serum levels. Among the seven tested SNPs, four polymorphisms: IFN-A rs10757212, IFN-A rs3758236, IFN-G rs2069705, IFN-G rs2069718, as well as INF-G rs1861493A/rs2069705A/rs2069718G haplotype were significantly associated with a predisposition for MCTD. Raynaud’s phenomenon, erosive arthritis, swollen hands and fingers, and sclerodactyly were significantly more frequently observed in MCTD patients with IFN-G rs2069718 G allele than in patients with IFN-G rs2069718 A allele. We also found that anti-U1-A autoantibodies most frequently occurred in MCTD patients with rs2069718 GA genotype, while the IFN-G rs2069705 AG and rs2069718 GA genotypes might be a marker of anti-Ro60 presence in MCTD patients. Our results indicate that IFN-G genetic variants may be potential genetic biomarkers for MCTD susceptibility and severity.